Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure.